Twice-weekly induction with ixazomib-lenalidomide-dexamethasone (IRd) combination followed by extended IRd consolidation and lenalidomide maintenance in transplant-eligible patients with newly diagnosed multiple myeloma: Results of the phase 2 study IFM2014-03

Br J Haematol. 2024 Sep;205(3):891-899. doi: 10.1111/bjh.19570. Epub 2024 May 29.

Abstract

Therapeutic strategies for patients with newly diagnosed multiple myeloma (NDMM) have considerably improved during the last 10 years. The IFM2014-03 trial proposed an all-oral triplet induction/consolidation regimen in transplant-eligible NDMM patients, followed by lenalidomide maintenance. Induction consisted of three 21-day cycles of ixazomib, lenalidomide and dexamethasone (IRd), before high-dose Melphalan with transplant followed by eight 28-day cycles of IRd consolidation before 13 cycles of lenalidomide maintenance. Forty-six patients were enrolled and received at least one dose of therapy, and 39 entered the maintenance phase. The primary end-point was stringent complete response after consolidation, and was achieved in nine patients (20.9%, 90% CI 11.4-33.7; p = 0.998). Ten patients (24.4%) had an undetectable minimal residual disease. The overall response rate was 95.7%. The 3-year progression-free survival was 66.3%. No unexpected toxicities were recorded, and only eight patients suspended from any study drug. Of note, 21 (45.7%) patients reported peripheral neuropathy (PN) (grades 1-2 with no serious adverse events). IRd induction and consolidation with transplant before lenalidomide maintenance shows lower response rates compared to other triplet therapies. It could be an alternative for patients who require an all-oral regimen and/or with pre-existent PN, especially if quadruplet regimens including anti-CD38 antibody are not available.

Keywords: clinical trials; multiple myeloma; transplant.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Boron Compounds* / administration & dosage
  • Boron Compounds* / adverse effects
  • Boron Compounds* / therapeutic use
  • Consolidation Chemotherapy / methods
  • Dexamethasone* / administration & dosage
  • Dexamethasone* / adverse effects
  • Dexamethasone* / therapeutic use
  • Female
  • Glycine* / administration & dosage
  • Glycine* / adverse effects
  • Glycine* / analogs & derivatives
  • Glycine* / therapeutic use
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Lenalidomide* / administration & dosage
  • Lenalidomide* / adverse effects
  • Lenalidomide* / therapeutic use
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / mortality

Substances

  • Lenalidomide
  • Dexamethasone
  • Glycine
  • ixazomib
  • Boron Compounds